PDF(Pubmed)
Abstract：
Overnutrition and genetic predisposition are major risk factors for various metabolic disorders. Stearoyl-CoA desaturase-1 (SCD1) plays a key role in these conditions by synthesizing unsaturated fatty acids (FAs), thereby promoting fat storage and alleviating lipotoxicity. Expression of SCD1 is influenced by various saturated and cis-unsaturated FAs, but the possible role of dietary trans FAs (TFAs) and SCD1 promoter polymorphisms in its regulations has not been addressed. Therefore, we aimed to investigate the impact of the two main TFAs, vaccenate and elaidate, and four common promoter polymorphisms (rs1054411, rs670213, rs2275657, rs2275656) on SCD1 expression in HEK293T and HepG2 cell cultures using luciferase reporter assay, qPCR and immunoblotting. We found that SCD1 protein and mRNA levels as well as SCD1 promoter activity are markedly elevated by elaidate, but not altered by vaccenate. The promoter polymorphisms did not affect the basal transcriptional activity of SCD1. However, the minor allele of rs1054411 increased SCD1 expression in the presence of various FAs. Moreover, this variant was predicted in silico and verified in vitro to reduce the binding of ETS1 transcription factor to SCD1 promoter. Although we could not confirm an association with type 2 diabetes mellitus, the FA-dependent and ETS1-mediated effect of rs1054411 polymorphism deserves further investigation as it may modulate the development of lipid metabolism-related conditions.
摘要：
营养过剩和遗传易感性是各种代谢紊乱的主要危险因素。硬脂酰辅酶A去饱和酶-1（SCD1）通过合成不饱和脂肪酸（FA）在这些条件下发挥关键作用，从而促进脂肪储存和减轻脂毒性。SCD1的表达受各种饱和和顺式不饱和脂肪酸的影响，但是饮食反式脂肪酸（TFA）和SCD1启动子多态性在其法规中的可能作用尚未得到解决。因此,我们的目的是调查两种主要TFA的影响，接种疫苗和elaidate，和四个常见的启动子多态性（rs1054411，rs670213，rs2275657，rs2275656）在HEK293T和HepG2细胞培养物中的SCD1表达使用荧光素酶报告分析，qPCR和免疫印迹。我们发现elaidate显著提高了SCD1蛋白和mRNA水平以及SCD1启动子活性,但不会因接种疫苗而改变。启动子多态性不影响SCD1的基础转录活性。然而,在存在各种FAs的情况下，rs1054411的次要等位基因增加了SCD1的表达。此外，该变体在计算机模拟中进行了预测,并在体外验证可降低ETS1转录因子与SCD1启动子的结合.虽然我们无法确认与2型糖尿病的关系，rs1054411多态性的FA依赖性和ETS1介导的作用值得进一步研究,因为它可能调节脂质代谢相关疾病的发展.
